DESCRIPTION: (Applicant's Abstract) Cannabis preparations are the most commonly used illicit substances in the United States. In recent years, rates of marijuana use and, in turn, dependence have been rising, especially among younger people. Heavy and chronic use of marijuana carries with it substantial morbidity. In the years to come, cannabis dependence will likely become an even more severe and prevalent health problem. Compared to other substances of abuse, the treatment of heavy and chronic marijuana use (dependence) has received comparatively little investigation. There are very few controlled treatment trials for cannabis dependence. Recent animal and human laboratory studies have characterized substantial withdrawal symptoms associated with the abrupt cessation of marijuana. These symptoms are characterized by a range of effects that include anxiety, irritability, somatic complaints, and difficulty sleeping. The symptoms associated with marijuana withdrawal resemble both depression and nicotine withdrawal, suggesting the utility of a pharmacological intervention. We propose a carefully constructed double-blind placebo-controlled trial testing two agents, bupropion and nefazodone, in the context of psychosocial intervention. We hypothesize that reducing withdrawal symptoms will result in greater retention in treatment and lead to higher rates of abstinence in treatment seeking marijuana users.